SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Cyanide is a toxic compound which inhibits the cellular utilization of oxygen. A number of substances can give rise to cyanide intoxication, which in some cases may have a delayed onset. The symptoms are non-specific and reflect cellular hypoxia. Several strategies may be employed in the treatment. Hydroxycobalamine is an effective and non-toxic antidote. On the basis of a case story, the toxicology, symptoms and treatment of cyanide poisoning are discussed.
Ten cases of pernicious anaemia seen over a 15-year period (1973-1988) in a Lagos hospital are presented. Their ages ranged from 34 to 67 with a mean of 53.6 years. Females outnumbered males 6 to 4. Complications seen include gastric carcinoma, myelopathy, peripheral neuropathy, skin hyperpigmentation, hair depigmentation and diarrhoea. Reluctance to consider the diagnosis owing to firmly held notions of its rarity and a penchant for empirically treating chronic anaemias with all available haematinics and blood transfusion are probably contributory to its underdiagnosis. The fact that seven of the patients presented were seen in the last three years and three of them in the last one year raises the possibility of an increasing incidence of pernicious anaemia in Africans. The disease may be much less rare in Africans than once believed, and medical education should emphasize its existence and advocate greater care in the management of chronic anaemias.
Explore the source record for details and available documents.
BACKGROUND: Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes. OBJECTIVES: To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders. METHODS: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members. RESULTS: Partial TC-II deficiency was found in 19 subjects. Apo TC-II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency. CONCLUSIONS: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances--despite normal serum vitamin B12 levels. Low serum UBBC and apo TC-II should confirm the diagnosis. Early vitamin B12 therapy may prevent irreversible neurologic damage.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Vitamin B12 deficiency causes decreased Methionine Synthase and L-Methylmalonyl-CoA Mutase activity and results in accumulation of Homocysteine, Methylmalonic acid and Propionylcarnitine. Propionylcarnitine is included in tandem mass spectrometry-based newborn screening programs for detection of certain inborn errors of metabolism. We report two asymptomatic newborns with Vitamin B12 deficiency due to maternal deficiencies. One was detected incidentally at 3 weeks of age; the second on supplemental newborn screening based on elevated Propionylcarnitine at 2 days of age. This illustrates the potential for false negative results for Vitamin B12 deficiency screening by acylcarnitine profiling in newborn screening. Homocysteine and Methylmalonic acid may be better markers of Vitamin B12 deficiency. In conclusion, we suggest measuring Methylmalonic acid, Propionylcarnitine and Homocysteine levels in blood spots in expanded newborn screening in order to detect asymptomatic newborns with Vitamin B12 deficiency. Further studies are needed to establish the sensitivity of these three markers in screening for Vitamin B12 deficiency.
Vitamin B12 and folate deficiencies are the main nutritional determinants of hyperhomocysteinemia, which is an independent risk factor for cardiovascular diseases. There is scarce information about nutritional status on vitamin B12 and serum levels of folate in Mexican older people. The objective was to evaluate the nutritional status of vitamin B12 and folic acid concentration in non-institutionalized, urban elderly men and women subjects. One hundred volunteers over 60 years were included in this cross-sectional study. Serum levels of vitamin B12 and folate were measured. In addition some biochemical and anthropometric indicators were also evaluated. Considering serum values of vitamin, 30% had vitamin B12 deficiency, 52% normal status and 18% with high levels. None subjects had folic acid deficiency, by the contrary, a high proportion (62%) showed elevated levels in serum. There was an effect of sex on vitamin B12 status. Elderly men showed significantly lower levels of vitamin B12, and it was according with significant higher prevalence of vitamin B12 deficiency in this group as compared with the women group. The high proportion of vitamin B12 deficiency found in this study underline a possible public health problem and guarantee further survey-studies about vitamin B12 status and to explore causes and consequences of the deficiency. Finally, due the sample size and the design of the study, the results must be seen with caution and not try to generalize.
The administration in vivo of the cobalamin analogue hydroxycobalamin[c-lactam] inhibits hepatic L-methylmalonyl-CoA mutase activity. The current studies characterize in vivo and in vitro the hydroxycobalamin[c-lactam]-treated rat as a model of disordered propionate and methylmalonic acid metabolism. Treatment of rats with hydroxycobalamin[c-lactam] (2 micrograms/h by osmotic minipump) increased urinary methylmalonic acid excretion from 0.55 mumol/day to 390 mumol/day after 2 weeks. Hydroxycobalamin[c-lactam] treatment was associated with increased urinary propionylcarnitine excretion and increased short-chain acylcarnitine concentrations in plasma and liver. Hepatocytes isolated from cobalamin-analogue-treated rats metabolized propionate (1.0 mM) to CO2 and glucose at rates which were only 18% and 1% respectively of those observed in hepatocytes from control (saline-treated) rats. In contrast, rates of pyruvate and palmitate oxidation were higher than control in hepatocytes from the hydroxycobalamin[c-lactam]-treated rats. In hepatocytes from hydroxycobalamin[c-lactam]-treated rats, propionylcarnitine was the dominant product generated from propionate when carnitine (10 mM) was present. The addition of carnitine thus resulted in a 4-fold increase in total propionate utilization under these conditions. Hepatocytes from hydroxycobalamin[c-lactam]-treated rats were more sensitive than control hepatocytes to inhibition of palmitate oxidation by propionate. This inhibition of palmitate oxidation was partially reversed by addition of carnitine. Thus hydroxycobalamin[c-lactam] treatment in vivo rapidly causes a severe defect in propionate metabolism. The consequences of this metabolic defect in vivo and in vitro are those predicted on the basis of propionyl-CoA and methylmalonyl-CoA accumulation. The cobalamin-analogue-treated rat provides a useful model for studying metabolism under conditions of a metabolic defect causing acyl-CoA accretion.
Explore the source record for details and available documents.
A 15-year old Chinese boy was diagnosed to have Leber's hereditary optic neuropathy (LHOA), having manifested with typical findings of bilateral severe visual loss and telangiectasia at the optic disc. However, no family history was elicited and an interval of more than 5 years separated visual loss in the two eyes. The latter is an extremely uncommon finding. Visual improvement was rapid and marked after instituting intramuscular hydroxycobalamine 5 mg weekly. Bilateral improvement of Snellen acuity to 6/9 was achieved within 6 months. This is also unusual in that visual prognosis is generally poor in LHOA, although spontaneous remissions have occasionally been recorded. In addition, the eye with a longer history of poor vision responded to therapy first.
The kinetics of the reaction of cyanide with free aquocobalamin (H2OCbl) and with aquocobalamin bound to a vitamin B12-binding protein (haptocorrin) from chicken serum (HC-H2OCbl) have been investigated as a function of temperature and pH. The mechanism of replacement of H2O from protein-bound and free H2OCbl is apparently the same and involves attack of both CN- (k1) and HCN (k2). The reactions with HC-H2OCbl are somewhat slower than those with free H2OCbl, k1 being 22-fold smaller and k2 7-fold smaller at 25 degrees C. The relatively small effect of the protein on the rate constants supports the view that the metal in HC-H2OCbl is readily accessible to solvent. Activation parameters suggest that the transition states for ligand substitution are stabilized by nucleophilic participation (at least by CN-) and that ligand substitution on the protein-bound cobalamin proceeds through more ordered, concerted transition states. The latter effect suggests that the Co-O bond of H2OCbl is strengthened upon binding to the haptocorrin.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A case of pernicious anaemia recurring after 14 years in a patient who had suspended parenteral vitamin B12 treatment two months after the first hospitalisation is described. The earliest haematological signs of vitamin B12 deficiency are examined and the apparent failure to absorb the vitamin B12 regularly taken with the diet when no longer administered parenterally is discussed.
Four cobalamines (methyl-, hydroxy-, adenosyl- and cyancobalamines) are considered as natural forms of vitamin B12 in human and animal tissues. Methyl- and adenosylcobalamines are the coenzymes of more than 10 enzymes, catalyzing important reactions of lipid, carbohydrate and protein metabolism. The four natural forms of vitamin B12 are interconverted in presence of corresponding enzymatic systems. Content of individual forms of cobalamines and of corresponding coenzymes depends on the function of enzymatic systems involved in their synthesis as well as on the enzymes, which use these derivatives as coenzymes. Spectra of cobalamines in human and animal bodies are dynamic systems, distinctly and specifically responding to various effects. The data on the ratio of individual forms of vitamin B12 in human and animal blood and tissues as well as their alterations under physiological and pathological conditions are discussed. Differentiation of individual physiologically active forms of vitamin B12 and their estimation is very important and may contribute to elucidation of molecular mechanisms of impairments in cobalamine metabolism in various diseases.